Macrophage-Secreted Factors Impair Human Adipogenesis: Involvement of Proinflammatory State in Preadipocytes
Abstract
Obesity is considered a chronic low-grade inflammatory state. The white adipose tissue produces a variety of inflammation-related proteins whose expression is increased in obese subjects. The nonadipose cell fraction, which includes infiltrated macrophages, is a determinant source of inflammation-related molecules within the adipose tissue. Our working hypothesis is that macrophage infiltration affects fat expansion through a paracrine action on adipocyte differentiation. Human primary preadipocytes were then differentiated in the presence of conditioned media obtained from macrophages differentiated from blood monocytes. Preadipocytes treated by macrophage-conditioned medium displayed marked reduction of adipogenesis as assessed by decreased cellular lipid accumulation and reduced gene expression of adipogenic and lipogenic markers. In addition to this effect, the activation of macrophages by lipopolysaccharides stimulated nuclear factor κB signaling, increased gene expression and release of proinflammatory cytokines and chemokines, and induced preadipocyte proliferation. This phenomenon was associated with increased cyclin D1 gene expression and maintenance of the fibronectin-rich matrix. Anti-TNFα neutralizing antibody inhibits the inflammatory state of preadipocytes positioning TNFα as an important mediator of inflammation in preadipocytes. Strikingly, conditioned media produced by macrophages isolated from human adipose tissue exerted comparable effects with activated macrophages, i.e. decreased adipogenesis and increased inflammatory state in the preadipocytes. These data show that macrophage-secreted factors inhibit the formation of mature adipocytes, suggesting possible role in limiting adipose tissue expansion in humans.
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In athletes, regular training induces a reduction in CRP concentration.
“Nevertheless, two longitudinal studies in athletes show that regular training induces a reduction in CRP concentration (211,212) .”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [212]
Recent data provided by our team showed that human pre-adipocytes in contact with activated macrophage media display a fibroblastic-like appearance, significantly proliferate and acquire pro-inflammatory properties.
“Recent data provided by our team showed that human pre-adipocytes in contact with activated macrophage media display a fibroblastic-like appearance, significantly proliferate and acquire pro-inflammatory properties [42].”
From Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity (2008) · cites this paper as [42]
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- Authors
- Lacasa, D., Taleb, S., Keophiphath, M., Miranville, A., & Clement, K.
- Affiliations
- Inserm (FR)
- Goethe University Frankfurt (DE)
- ORCID
- Taleb, Soraya
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2007-02-01
- Volume
- 148
- Issue
- 2
- Pages
- 868-877
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2121845219
- Cited by
- 334
- References
- 42
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 12 · 2023: 10 · 2022: 12 · 2021: 19 · 2020: 14 · 2019: 10 · 2018: 15 · 2017: 18 · 2016: 19 · 2015: 12 · 2014: 19 · 2013: 22 · 2012: 16
- FWCI
- 17.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Institut National de la Santé et de la Recherche Médicale
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- adipogenesis, preadipocytes, obesity, low-grade inflammation, macrophage infiltration, paracrine signaling, TNF-α, NF-κB signaling, lipopolysaccharide, inflammatory cytokines, chemokines, cyclin D1, adipose tissue expansion
- MeSH terms
- Adipose Tissue, Cell Differentiation, Cells, Cultured, Culture Media, Female, Humans, Inflammation, Lipopolysaccharides, Macrophages, Stem Cells, Signal Transduction, Biomarkers, Gene Expression, Cytokines, NF-kappa B, Adipocytes, Inflammation Mediators, Chemokines, Cyclin D1, Cell Proliferation, Adipogenesis, Lipid Metabolism
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